1. Field of Invention
The present invention relates generally to the treatment of immunodeficiency diseases, and in particular to an immunotherapy treatment for a patient suffering from the acquired immune deficiency syndrom (AIDS).
2. Status of Prior Art
An antigen is any substance which when introduced into a host animal or human provokes an immune response leading to acquired immunity. Where the immune response is deficient or malfunctions, this results in an immunodeficiency disorder.
An antigen may be a soluble substance (i.e., a bacterial toxin or serum protein) or it may be particulate in nature, such as a bacterial cell. In general, the greater the degree to which an antigen, in terms of its chemical composition and structure, is "foreign" to the individual being immunized, the greater its effectiveness in stimulating an immune response. A substance that acts as an antigen, whether a virus, a bacteria or a body cell, has on its surface and in some instances in its interior, a number of reactive sites or determinants. It is these determinants or epitopes that impart specificity to the immune response, for they constitute the sites that react with an antibody or a sensitized lymphocyte.
The immune response gives rise either to the formation of specific antibodies that circulate in the blood stream (humoral immunity) or to an increase in the number of specifically reactive cells, called lymphocytes (cell-medicated immunity), or to both. These specific antibodies and specialized lymphocytes both react to the antigen functioning as the immunizing agent. Immunity acquired in this manner makes it possible for the body to destroy or neutralize invading pathogenic microbes or other toxins. Accordingly, an individual's acquired immunity serves as his principal line of internal defense against pathogens.
Lymphocytes (white blood cells) are the precursor cells of both humoral and cell-mediated immunity. In the human body, one finds a pool of recirculating lymphocytes which flows from the blood system into the lymph nodes, the spleen and other tissues, and then back to the blood system by way of the major lymphatic channels. High concentrations of lymphocytes are found in the lymph nodes as well as at those sites where they are manufactured and processed: the bone marrow, the thymus and the spleen.
Stem cells existing in bone marrow have the potential to develop in a number of directions depending on various factors which influence their development. Thus, some develop into red blood cells and others into different types of white blood cells. The stem cells involved in immune responses differentiate into either B-type or T-type lymphocytes.
Thus, there are two main classes of lymphocytes involved in the immune system of humans and animals; namely, T-cells and B-cells. The first class, T-cells, are thymus derived, and are differentiated in this gland from stem cells. The thymus may be regarded as the master gland in the body's immune system. When they are present within this gland, the differentiating cells are terms "thymocytes." When processed to maturity, the T-cells then emerge from the thymus and circulate among the tissues, lymphatics and bloodstream and thereby form a large proportion of the recirculating small lymphocytes. Only about 20 percent of the recirculating pool is constituted by B-cells.
The T-cell class of lymphocytes have immunological specificity and are directly engaged as effector cells in the cell-mediated immune response. These effector cells behave as through they possess antibody-like molecules on their surface; and when they react with the inducing antigen, they bring about cytotoxic effects on cells, including those containing viral antigens. These effector cells are also responsible for graft rejection, for they react with foreign cells from the graft. Though T-cells do not secrete humoral antibodies, they are sometimes required for the stimulation of B-cells to enhance the production of antibodies. Moreover, T-cells can enlist the aid of macrophages in destroying pathogens.
The second class of lymphocytes, B-cells, are derived from bone marrow and are responsible for the humoral immunity response; for after contact with an antigen, they give rise to antibody-producing plasma cells. However, while they also develop from stem cells, B-type lymphocytes are capable of forming memory cells. These are long-lived, resting lymphocytes that have been so primed by prior contact with an antigen that upon renewed contact with the same antigen they produce a secondary immune response. This response is faster and more vigorous than the primary response and enables an individual who had previously been exposed to a pathogen to respond much more effectively in a subsequent encounter with this pathogen.
Microbiologists now recognize that T-cells, the first class of lymphocytes, can be divided into at least three subclasses termed "helper," "suppressor," and "killer" T-cells. "Helper" T-cells are those which act to promote a reaction, whereas "Suppressor" T-cells suppress a reaction. "Killer" T-cells are characterized by their "lysing" properties; that is, their ability to kill foreign cells.
The sub-classes for T-cells in human systems are described in greater detail by Chess and Schlossman in "Functional Analysis of Distinct Human T-Cell Subsets Bearing Unique Differentiation Antigens" (Contemporary Topics in Immunobiology--O. Stutman, Editor, Plenum Press 1977, Vol. 7, 363-379).
In the proper diagnosis or treatment of immunodeficiency disorders or conditions, the ability to correctly identify or suppress classes or sub-classes of lymphocytes is vital. See, for example, Aisenberg et al., The American Journal of Medicine 58:300--March 1975.
Thus, certain leukemias and lymphomas differ in their prognosis, depending on whether they are of the B-cell or T-cell origin; hence an evaluation of the disease prognosis makes it necessary to distinguish between these two classes of lymphocytes. In certain leukemias, excess T-cells are produced in an arrested stage of development, and proper diagnosis then depends on the ability to detect this imbalance.
The main concern of the present invention is with the acquired immune deficiency syndrome (AIDS) caused by a breakdown in the immunity response. This is attributed to the depletion of "helper" type T-cells which are killed by a human virus that is probably of African origin (See: Barre-Sinoussi et al., "Isolation of a T-lymphotropic Retrovirus From a Patient At Risk for Acquired Immune Deficiency Syndrome (AIDS)"--Science 1983; 220: 868-871).
The virus which causes AIDS, formerly identified as HTLV-III (human T-lymphotropic virus type III) or as LAV (lymphadenopathy-associated virus) or ARV (AIDS-related virus), has by a decision of the International Committee on Taxonomy of Virus designated this virus as HIV (human immunodeficiency virus).
AIDS is a recently recognized disease that is now evident in several parts of the world. Its overwhelming prevalence among homosexual men with multiple sexual partners, illegal intravenous drug abusers, hemophiliacs, blood transfusion recipients, and close heterosexual contacts of members of these high-risk groups strongly suggests that the disease spreads by the transmission of an infectious agent. The primary targets of affliction in the human body are specific subpopulations of T-cells. The severe immune deficiency of these patients results from an unusually low proportion of helper T-cells (T4) in their lymphocyte population, thereby reducing the availability of many T4 helper functions, among which is the production of antibodies by B-cells.
Those who suffer from AIDS become susceptible to a variety of rare illnesses. Most commonly found in AIDS patients are pneumocystis carinii pneumonia, a parasite-induced lung infection, and Kaposi's sarcoma, a rare form of cancer or tumor of the blood vessel walls.
Various types of antiviral drugs are presently undergoing tests, including the experimental drug azidothymidine (AZI). Currently there are no antiviral drugs that have been proven to cure AIDS or to ameliorate this condition. No drug for AIDS treatment has yet been accepted by the Federal Food and Drug Administration.